EP2334269A1 - Steuerprogramm zum steuern elektromagnetischer strahlung für eine quervernetzung von augengewebe - Google Patents
Steuerprogramm zum steuern elektromagnetischer strahlung für eine quervernetzung von augengewebeInfo
- Publication number
- EP2334269A1 EP2334269A1 EP09778460A EP09778460A EP2334269A1 EP 2334269 A1 EP2334269 A1 EP 2334269A1 EP 09778460 A EP09778460 A EP 09778460A EP 09778460 A EP09778460 A EP 09778460A EP 2334269 A1 EP2334269 A1 EP 2334269A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- change
- control program
- tissue
- electromagnetic radiation
- eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 238000004132 cross linking Methods 0.000 title claims description 38
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 42
- 238000005259 measurement Methods 0.000 claims abstract description 24
- 230000008859 change Effects 0.000 claims description 62
- 210000004087 cornea Anatomy 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 36
- 230000005855 radiation Effects 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 21
- 230000002123 temporal effect Effects 0.000 claims description 5
- 230000003204 osmotic effect Effects 0.000 claims description 4
- 208000031816 Pathologic Dilatation Diseases 0.000 claims description 3
- 230000004075 alteration Effects 0.000 claims description 3
- 210000002159 anterior chamber Anatomy 0.000 claims description 3
- 230000003054 hormonal effect Effects 0.000 claims description 3
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- 208000029091 Refraction disease Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
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- 230000004430 ametropia Effects 0.000 description 1
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Classifications
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/50—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
- G16H20/40—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
- A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
- A61B3/107—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for determining the shape or measuring the curvature of the cornea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
- A61F2009/00872—Cornea
Definitions
- the invention relates to a control program for controlling a source of electromagnetic radiation with which a patient's eye tissue crosslinks by means of a photosensitizer introduced into the tissue, and a method for producing such a control program, and a method for determining whether a patient for an ophthalmological Treatment with cross-linking of eye tissue by means of electromagnetic radiation and a photosensitizer is suitable.
- the human eyeball is bounded by the outer eye skin. Due to the intraocular pressure, the collagen-containing outer eye skin is stretched and gives the healthy eyeball an approximately spherical shape.
- the outer eye skin consists of the white dermis (sclera).
- the front area is the visible light permeable cornea (cornea).
- Deformations of the outer eye skin can be the cause of ametropia.
- a form of myopia the axis myopia
- An ellipsoidal surface of the cornea may result in a form of astigmatism, also referred to as corneal curvature.
- Another disease of the cornea is called keratoconus.
- keratoconus as a result of abnormal softening of the cornea, there is a progressive thinning and conical deformation of the cornea of the eye. As the bulge increases, the cornea below the center becomes thinner. It can break through and scar. This permanently reduces the visual acuity.
- the causes of keratoconus are still largely unknown today. He occurs familial heaped up, which among other things speaks for a genetic disposition. Another risk factor for the development of keratoconus is atopias such as allergic diseases.
- the conventional therapy of advanced keratoconus is to remove the diseased cornea and replace it with an allograft.
- an organ transplantation with the associated risks and complications. Adequate vision is often achieved approximately two years after surgery.
- the corneal transplantation concerns In keratoconus mostly young people, why the graft must work properly for decades.
- An improved therapy of keratoconus stabilizes the cornea by cross-linking.
- the treatment allows photochemical, non-tissue-removing stabilization or alteration of the biomechanical and biochemical properties of the cornea.
- the treatment principle is also applicable to other affected regions of the eye.
- a photosensitizer solution is introduced into the eye tissue to be changed and exposed to primary radiation.
- the primary radiation used is electromagnetic radiation in the wavelength range from about 300 nm to 800 nm (UV-A radiation or visible light).
- a device serves to solidify the sclera located in the posterior segment of the eye.
- the primary radiation can act on the sclera through the interior of the eye or by lying on the outside pillows.
- a photomediator or photosensitiser causes cross-linking in the sclera. This counteracts scleral growth and prevents progression of axonal myopia.
- WO 2008/000478 A1 describes an irradiation system for the biomechanical stabilization of the cornea.
- cross-linking to the cornea can be effected in conjunction with a photosensitizer.
- Irradiation system offers the possibility to treat specific diseases, such as keratoconus.
- Crosslinking performed by photosensitizing may also be undesirable, leading to damage to ocular tissue or to the function of the eye.
- the object of the invention is to provide methods and control programs with which an evaluation of the effect of cross-linking can be estimated as reliably as possible in advance of any ophthalmological intervention.
- the invention provides a method for generating a control program for controlling a source of electromagnetic radiation, with which a cross-linking is carried out in the eye tissue of a patient by means of a photosensitizer introduced into the tissue in order to change the eye tissue with respect to its shape and / or at least to effect one of its mechanical properties, with the following steps:
- b) in a computer is simulated with the measurement data and treatment parameters, which include a predetermined auxiliary control program for controlling the source of electromagnetic radiation, a result regarding the achieved with these treatment parameters change in the eye tissue,
- step c) the thus simulated change is compared with an alteration of the ocular tissue to be achieved, d) then, if step c) results in a sufficient match between the simulated change and the ocular tissue change to be achieved, the auxiliary control program scheduled in step b) is selected as the control program to be generated, and e) if in step c ) the comparison does not give a sufficient correspondence between the simulated change and the change in the eye tissue to be achieved, at least one of the treatment parameters in step b) is modified and steps b), c) and d) are then carried out again.
- step a) one or more of the following data is used as measurement data: the corneal topography of the patient's eye; the shape of the back surface of the cornea; other shape characteristics of the front and / or back surface of the cornea, such as depressions or elevations, biomechanical properties of the cornea, such as their stability; the corneal thickness; the eye length; the depth and / or volume of the anterior chamber; Results of wavefront measurements; age; Gender; hormonal status of the patient; the state of a given ectasia; Living habits (e.g., smoking) of the patient.
- the auxiliary control program takes into account one or more of the following variables: intensity of the irradiation with the electromagnetic radiation; Concentration of the photosensitizer in the tissue; the osmotic characteristic of the photosensitizer; the irradiation time; the period of application of the photosensitizer before irradiation; the periods of application of the photosensitizer during irradiation; the type of electromagnetic radiation (e.g., continuous or pulsed) including the radiation parameters, such as the wavelength; the tactile rate of gepuister radiation; the spatial and temporal control of the radiation.
- intensity of the irradiation with the electromagnetic radiation Concentration of the photosensitizer in the tissue; the osmotic characteristic of the photosensitizer; the irradiation time; the period of application of the photosensitizer before irradiation; the periods of application of the photosensitizer during irradiation
- the type of electromagnetic radiation e.g., continuous or pulsed
- the radiation parameters such
- control program for controlling electromagnetic radiation for performing cross-linking in ocular tissue, wherein the control program is generated with the following steps:
- a 1 ) measurement data relating to the patient and the eye are obtained, b 1 ) in a computer, with the measurement data and treatment parameters which contain a predefined auxiliary control program for controlling the source of electromagnetic radiation, a result with respect to the change in the eye tissue achieved with these treatment parameters is simulated, c 1 ) the change thus simulated becomes compared with a change in ocular tissue to be achieved, d 1 ) if step c ') gives a sufficient correspondence between the simulated change and the ocular tissue change to be achieved, the auxiliary control program scheduled in step b 1 ) is determined to be the one to be generated Control program is selected, and e 1 ) if, in step c 1 ), the comparison does not result in a sufficient agreement between the simulated change and the change in the eye tissue to be achieved, at least one of the treatment parameters in step b 1 ) is modified, and then the Steps b 1 ), c 1 ) and d ') are carried out again.
- the invention determines whether a patient is at all suitable for an ophthalmological procedure by means of cross-linking.
- the invention provides a method for determining whether a patient is suitable for ophthalmological treatment with cross-linking of eye tissue by means of electromagnetic radiation and by means of a photosensitizer, with the following steps: a) Measurement data relating to the patient and the eye are obtained .
- a computer in a computer is simulated with the measurement data and treatment parameters, which include a predetermined auxiliary control program for controlling the source of electromagnetic radiation, a result regarding the achieved with these treatment parameters change in the eye tissue,
- the auxiliary control program provides, simultaneously with or after controlling the source of electromagnetic radiation for cross-linking, (second) controlling a source of electromagnetic radiation to change the eye tissue with regard to its shape and / or at least one of its mechanical properties by photothermal action, Photoablation and / or photodisruption.
- said source of electromagnetic radiation for photothermal action, photoablation and / or photodisruption may be a femtosecond laser or an excimer laser.
- FIG. 1 shows schematically a block diagram for carrying out the invention in its full scope
- Figure 2 shows schematically a block diagram of the embodiment of the invention to a limited extent
- Figure 3 is a block diagram illustrating the method of the invention for generating a control program for the control of electromagnetic radiation in cross-linking
- FIG. 4 schematically shows an empirically observed relationship with respect to light attenuation by photosensitizer and cornea as a function of corneal depth
- FIG. 5 schematically illustrates a measured increase in corneal biomechanical strength as a function of a calculated increase in polymer number in the cornea
- FIG. 6 schematically shows an observed refractive power change of the cornea one year after cross-linking as a function of a prediction criterion from measured pre-operative variables.
- a cross-linking in ophthalmology is understood to mean a photochemical influence on ocular tissue. The through this
- Influenced change may be in the biomechanical and biochemical properties of the tissue, but in particular also in a change in the shape of the tissue, in particular its shape and / or curvature. Stabilization of the tissue is also achieved by cross-linking, i. a change in its mechanical elasticity. For this purpose, in a conventional manner
- Photosensitizer i. a suitable chemical solution on and brought into the ocular tissue, which then causes together with the electromagnetic radiation, the photochemical processes in the tissue, which are addressed under the keyword “cross-linking".
- the effect of the electromagnetic radiation, also called “primary radiation”, on and in the tissue is neither thermal nor photoablative nor photodisruptive.
- the invention described in more detail below provides a method with which the complex relationships between the various properties of the electromagnetic radiation used (eg wavelength, intensity, distribution in space and time) and the various properties of the photosensitizer used (eg Nature, concentration, dilution, osmotic properties, time sequence of application, etc.) and the effect achieved in the eye tissue, in particular the cornea, can be determined at least approximately for each individual patient.
- the full application of the invention enables the obtaining of a control program with which electromagnetic radiation for cross-linking can be introduced into the ocular tissue.
- a control program in this sense includes the known in the art as such control of optical means by which laser radiation, for example via mirrors and other imaging optical elements, such as lenses, etc., can be directed to the eye to be treated, eg in shape a so-called “spot", ie a relatively small spot (with a diameter in relation to the overall dimensions of the eye) in the mm range), which is guided according to a predetermined program in space and time with respect to the eye.
- spot ie a relatively small spot (with a diameter in relation to the overall dimensions of the eye) in the mm range
- Other means are known in the art to introduce electromagnetic radiation into ocular tissue according to a desired program, such as rotating masks, moving apertures, etc.
- the irradiation system according to the international patent application PCT / EP2007 / 005740 (abovementioned publication WO 2008/000478 A1) can be used as a device for carrying out the present invention and for controlling electromagnetic radiation on an eye.
- This known radiation system for ophthalmological applications is assumed to be expressly known for carrying out the present invention.
- FIG. 1 schematically illustrates the input variables for the method according to the invention for generating a control program and the results obtained after carrying out the method.
- the method is iterative when fully executed, i. starting from a relatively general auxiliary control program, this initial auxiliary control program is successively loop-by-loop (ie iterative) improved until the properties of the control program thus generated correspond to the desired expectations taking into account the characteristics of the patient and his eye.
- treatment parameters include the above-mentioned initial auxiliary control program with which the iteration process can be started.
- Treatment goals are e.g. the desired therapeutic changes in the shape and / or the mechanical properties of the eye tissue to be treated, in particular the cornea.
- treatment parameters include, in particular, the following variables which the auxiliary control program uses as data to be considered: intensity of the irradiation with the electromagnetic radiation; Concentration of the photosensitizer in the tissue; the osmotic characteristic of the photosensitizer; the irradiation time; the period of application of the photosensitizer before the radiation; the periods of application of the photosensitizer during irradiation; the type of electromagnetic radiation (eg continuous or pulsed) including the radiation parameters, such as wavelength; the sampling rate with pulsed radiation; the spatial and temporal control of the radiation.
- intensity of the irradiation with the electromagnetic radiation include, in particular, the following variables which the auxiliary control program uses as data to be considered: intensity of the irradiation with the electromagnetic radiation; Concentration of the photosensitizer in the tissue; the osmotic characteristic of the photosensitizer; the irradiation time; the period of application of the photosensitizer before the radiation; the periods of application of the photosensit
- patient measurement data are in particular the following data: the corneal topography of the patient's eye; the shape of the back surface of the cornea; other shape characteristics of the front and / or back surface of the cornea, such as depressions or elevations; biomechanical properties of the cornea, such as their stability; the corneal thickness; the eye length; the depth and / or volume of the anterior chamber; Results of wavefront measurements; the age, sex, hormonal status of the patient; the state of a given ectasia; Living habits (e.g., smoking) of the patient.
- the above-mentioned data can each be entered individually or in any combination as “patient measurement data”.
- auxiliary control program initially receives so-called "boundary conditions" as input data.
- boundary conditions are in particular security relevant data, i. The requirements set out by the program in its implementation,
- the program enters the "treatment goals", i. the changes in ocular tissue to be made with the cross-linking in order to achieve a therapeutic effect.
- the treatment objectives thus consist in a desired change in the eye tissue with regard to its shape (shape / curvature) and / or its biomechanical properties, such as strength and stability.
- a particular application to be emphasized are treatment goals that are directed to selective biomechanical deformation of the cornea to correct refractive errors.
- changes in the shape of the cornea or Tissue structure given by the treatment goals and taken into account by corresponding target values of the auxiliary control program in the simulation advantageously goes beyond purely photochemical cross-linking and also includes a photothermal effect, photoablation and / or photodisruption induced by electromagnetic radiation (corrective irradiation).
- this extension requires no complex modifications to the irradiation system, but can be achieved only by a corresponding extension of the control program.
- the auxiliary control programs, and ultimately the control programs may schedule the corrective irradiation prior to, concurrent with, or subsequent to the photochemical treatment of the tissue by cross-linking.
- the (auxiliary) control program includes parameters and / or control signals for driving a femtosecond laser or an excimer laser for corrective treatment.
- One way to program the control program is to empirically determine the relationship between the input data mentioned (ie roughly: patient data, radiation data, photosensitizer data (see above) and the resulting change (effect) in the eye tissue and in the type of a "look-up table" in the program. This is possible using both a variety of suitable experimental animals as well as data obtained with a variety of patients.
- the respective effects (changes in the eye tissue) depending on the input simulating data provides for the use of theoretical concepts.
- These are in particular physical models for the photopolymerization process (cross-linking) in the form of mathematical descriptions of the individual sub-processes.
- Such physical models allow, for example, the simulation of the diffusion of the photosensitizer solution into the eye tissue by means of the diffusion equations.
- the effect of the electromagnetic radiation can also be modeled by calculating the absorption of the photons in the tissue and in the photosensitizer solution by means of the absorption equations known as such as a function of the cross-sections.
- such theoretical methods can be used to simulate the change in the shape of the ocular tissue as a function of the change in mechanical strength achieved, for example, by using finite element methods well known in mechanics.
- the program calculates the effect of the electromagnetic radiation, taking into account the input data, and then either the program or the user can estimate whether the simulated change in ocular tissue characteristics will be sufficient with the desired therapeutic changes to the ocular tissue matches. Tolerance values for the individual parameters can then be specified for the "sufficient match” and then, if the deviation lies within the tolerance values, can be recognized as "sufficient agreement”. If a sufficient match is detected, then the last used control program can be used as the sought to be generated control program for controlling the electromagnetic radiation and it can be carried out the treatment of the patient with it.
- the treatment parameters for example be employed for the next loop auxiliary control program is changed.
- the photosensitizer its concentration, temporal order, chemical nature, etc. may be changed, or properties of the electromagnetic radiation used in the simulation process may be changed, such as irradiation intensity, irradiation time, type of radiation (continuous or pulsed), including corresponding sample rate, etc., the wavelength of the radiation, the distribution of the radiation in space and time.
- the direction of change of these input treatment parameters may also be due in the program empirical experience can be given, for example, in the result of overcrossing in the previous loop, the irradiation intensity and / or the photosensitizer concentration can be reduced.
- the iterative process optionally after passing through multiple simulation loops, provides optimized treatment parameters including the control program for controlling the electromagnetic radiation, i. a program that contains all the essential parameters of electromagnetic radiation, such as intensity, distribution in space and time, wavelength, sampling rates, etc.
- the program provides optimal values regarding the parameters of the photosensitizer, such as chemical structure, concentration, temporal order, spatial order, etc.
- Figure 2 shows a simplified variant of the invention which makes it possible to judge, for a given patient, whether it is at all suitable for treatment of the type with crosslinking in question, using predetermined standard treatment parameters.
- the procedure is then not iterative, but consists of a single arithmetic loop using the standard treatment parameters, the patient's individual measurement data and constraints in the above sense.
- the change in eye tissue is calculated by simulation, and based on the simulated result, a statement is made as to whether the patient is suitable for cross-linked treatment.
- the abovementioned boundary conditions are used for this purpose, and it is determined whether the simulation result with respect to the boundary conditions reaches critical values.
- a depth of keratocyte damage by simulation may result which prohibits treatment of the patient by cross-linking with the standard treatment parameters.
- a change in the curvature of the cornea may result in the simulation, which is far from the desired treatment goal. This allows a user with relatively little hardware and hardware Software without possibility of changing the input treatment parameters, a selection of suitable for the treatment of patients.
- a limitation to the standard treatment parameters may also be required by a surge of experience of the surgeon or for regulatory reasons.
- FIG. 3 again summarizes schematically in a block diagram the essential features of the generation of the control program for controlling the radiation for the cross-linking.
- the diagram briefly illustrates the control program generation methods described above. Explicit examples of the quantities given in the diagram are given in the following table.
- the procedure is based on the patient-specific measurement data, which is included in the physical and empirical calculation models.
- the data set to be simulated is initially completed by the standard treatment parameters.
- the method is given one of the following objectives or a combination of the following objectives: maximizing a mechanical strength increase of the eye tissue, minimizing a time of treatment of the eye tissue, deformation of the eye tissue according to a predetermined structure and defined change of refractive index in ocular tissue.
- These treatment objectives are compared with the mechanical strength increase of the eye tissue calculated by the simulation, the deformation of the eye tissue immediately after the treatment, the deformation of the eye tissue as a function of the time of treatment or the refractive index in the ocular tissue.
- the mechanical strength increase and the refractive index are calculated as a function of a depth in the eye tissue.
- safety-related boundary conditions are prescribed for the process.
- a physico-chemical calculation model which indicates the polymer generation as a function of the local irradiation intensity I (t, ⁇ , y, z) and the locally applied photosensitizer concentration c (t, ⁇ , y, z).
- the local irradiation intensity takes into account the calculated light attenuation through the adhesion film of the (residual) photosensitizer solution on the surface Cornea.
- FIG. 5 schematically shows the empirically found relationship between biomechanical strength and calculated polymer number. A general tendency is that a higher polymer generation leads to a higher increase in strength, which is quantitatively described by the modulus of elasticity of the cornea.
- the keratocyte damage depth in the cornea is determined as one of the boundary conditions. Tabulated values of the keratocyte damage depth obtained in animal experiments are available.
- a prediction of the expected change in curvature as one of the treatment goals is also simulated and quantified by a numerical prediction criterion of the diopter change.
- the prediction criterion and other pre-operative patient data are linked to curvature changes already made, which are treated one year after the treatment in a statistically significant number of treated
- FIG. 6 schematically shows the empirical function which indicates the power change achieved after one year as a function of the numerical prediction criterion.
- the simplified procedure makes a decision against the treatment of the patient.
- the simulation is repeated on the basis of a systematic variation of the treatment parameters. This iterative process, when an upper limit of iterations is reached, will also be aborted with the decision to discontinue treatment of the patient Treatment goals / boundary conditions remain predicted to be missed by the simulation.
- the decision is made for the treatment of the patient.
- the treatment parameters most recently used in the simulation essentially represent the control program obtained.
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102008046834A DE102008046834A1 (de) | 2008-09-11 | 2008-09-11 | Steuerprogramm zum Steuern elektromagnetischer Strahlung für eine Quervernetzung von Augengewebe |
PCT/EP2009/006579 WO2010028830A1 (de) | 2008-09-11 | 2009-09-10 | Steuerprogramm zum steuern elektromagnetischer strahlung für eine quervernetzung von augengewebe |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2334269A1 true EP2334269A1 (de) | 2011-06-22 |
EP2334269B1 EP2334269B1 (de) | 2014-12-31 |
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ID=41479151
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP09778460.7A Active EP2334269B1 (de) | 2008-09-11 | 2009-09-10 | Steuerprogramm zum steuern elektromagnetischer strahlung für eine quervernetzung von augengewebe |
Country Status (5)
Country | Link |
---|---|
US (1) | US8887734B2 (de) |
EP (1) | EP2334269B1 (de) |
DE (1) | DE102008046834A1 (de) |
ES (1) | ES2529749T3 (de) |
WO (1) | WO2010028830A1 (de) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009073213A1 (en) | 2007-12-05 | 2009-06-11 | Avedro, Inc. | Eye therapy system |
US9707126B2 (en) | 2009-10-21 | 2017-07-18 | Avedro, Inc. | Systems and methods for corneal cross-linking with pulsed light |
WO2011050164A1 (en) | 2009-10-21 | 2011-04-28 | Avedro, Inc. | Eye therapy |
JP6377906B2 (ja) | 2010-03-19 | 2018-08-22 | アヴェドロ・インコーポレーテッドAvedro,Inc. | 眼治療を適用およびモニターするためのシステム |
EP2907490A1 (de) * | 2010-04-21 | 2015-08-19 | IROC Innocross AG | Vorrichtung für die vernetzung von okulärem gewebe mit elektromagnetischer strahlung |
DE102010020194B4 (de) * | 2010-05-07 | 2022-09-08 | Carl Zeiss Meditec Ag | Vorrichtung zur Stabilisierung der Augenhornhaut |
US9622911B2 (en) | 2010-09-30 | 2017-04-18 | Cxl Ophthalmics, Llc | Ophthalmic treatment device, system, and method of use |
US9044308B2 (en) | 2011-05-24 | 2015-06-02 | Avedro, Inc. | Systems and methods for reshaping an eye feature |
WO2012167260A2 (en) | 2011-06-02 | 2012-12-06 | Avedro, Inc. | Systems and methods for monitoring time based photo active agent delivery or photo active marker presence |
WO2013148895A1 (en) | 2012-03-29 | 2013-10-03 | Cxl Ophthalmics, Llc | Ocular cross-linking system and method for sealing corneal wounds |
WO2013148896A1 (en) | 2012-03-29 | 2013-10-03 | Cxl Ophthalmics, Llc | Ocular treatment solutions, delivery devices and delivery augmentation methods |
EP2830637A4 (de) | 2012-03-29 | 2016-03-16 | Cxl Ophthalmics Llc | Zusammensetzungen und verfahren zur behandlung oder prävention von erkrankungen im zusammenhang mit oxidativem stress |
US9498114B2 (en) | 2013-06-18 | 2016-11-22 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
WO2014205145A1 (en) | 2013-06-18 | 2014-12-24 | Avedro, Inc. | Systems and methods for determining biomechanical properties of the eye for applying treatment |
AU2013404375B2 (en) * | 2013-10-30 | 2017-08-03 | Alcon Inc. | Crosslinking control |
EP3105694A2 (de) * | 2014-02-13 | 2016-12-21 | The Cleveland Clinic Foundation | Vorhersage und verringerung des risikos von ectasia und optimierung von therapieergebnissen |
CN106572919B (zh) | 2014-06-27 | 2020-06-02 | Tec晶体有限责任公司 | 用于角膜胶原交联的实时声学剂量测定 |
CN107205845B (zh) | 2014-10-27 | 2020-03-31 | 艾维德洛公司 | 用于眼的交联治疗的系统和方法 |
US10114205B2 (en) | 2014-11-13 | 2018-10-30 | Avedro, Inc. | Multipass virtually imaged phased array etalon |
DE102014016990B3 (de) | 2014-11-18 | 2016-02-11 | Wavelight Gmbh | Düseneinheit zur Vernetzung von Augengewebe |
EP3827792A1 (de) | 2015-04-24 | 2021-06-02 | Avedro, Inc. | Systeme und verfahren zur lichtaktivierung eines an einem auge applizierten lichtsensibilisators |
WO2016191342A1 (en) | 2015-05-22 | 2016-12-01 | Avedro, Inc. | Systems and methods for monitoring cross-linking activity for corneal treatments |
CN108025011A (zh) | 2015-07-21 | 2018-05-11 | 艾维德洛公司 | 用光敏剂治疗眼睛的系统和方法 |
JP6679724B2 (ja) | 2015-12-03 | 2020-04-15 | アヴェドロ・インコーポレーテッドAvedro,Inc. | 眼をマスク装置で処置するためのシステムおよび方法 |
CA3052147A1 (en) | 2017-01-31 | 2018-08-09 | Optimedica Corporation | Methods and systems for laser ophthalmic surgery that provide for iris exposures below a predetermined exposure limit |
AU2019231257A1 (en) | 2018-03-05 | 2020-10-15 | Avedro, Inc. | System for eye tracking during eye treatment |
US11766356B2 (en) | 2018-03-08 | 2023-09-26 | Avedro, Inc. | Micro-devices for treatment of an eye |
US12016794B2 (en) | 2018-10-09 | 2024-06-25 | Avedro, Inc. | Photoactivation systems and methods for corneal cross-linking treatments |
WO2021026405A1 (en) | 2019-08-06 | 2021-02-11 | Avedro, Inc. | Photoactivation systems and methods for corneal cross-linking treatments |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5163934A (en) * | 1987-08-05 | 1992-11-17 | Visx, Incorporated | Photorefractive keratectomy |
US5740815A (en) * | 1995-06-07 | 1998-04-21 | Alpins; Noel A. | Method for surgically achieving minimum astigmatism measured refractively and topographically |
DE4232915A1 (de) * | 1992-10-01 | 1994-04-07 | Hohla Kristian | Vorrichtung zur Formung der Cornea durch Abtragen von Gewebe |
US5891131A (en) | 1993-02-01 | 1999-04-06 | Arizona Board Of Regents | Method and apparatus for automated simulation and design of corneal refractive procedures |
US5843070A (en) * | 1996-05-13 | 1998-12-01 | Partech, Inc. | Simulating corneal laser surgery |
DE19904753C1 (de) * | 1999-02-05 | 2000-09-07 | Wavelight Laser Technologie Gm | Vorrichtung für die photorefraktive Hornhautchirurgie des Auges zur Korrektur von Sehfehlern höherer Ordnung |
ES2390397T3 (es) | 1999-10-21 | 2012-11-12 | Technolas Perfect Vision Gmbh | Perfil corneal personalizado |
DE10022995C2 (de) * | 2000-05-11 | 2003-11-27 | Wavelight Laser Technologie Ag | Vorrichtung für die photorefraktive Hornhautchirurgie |
SG127691A1 (en) * | 2000-07-21 | 2006-12-29 | Univ Ohio State | Methods and instruments for improving refractive ophthalmic surgery |
WO2004091458A1 (en) * | 2003-04-11 | 2004-10-28 | Bausch & Lomb Incorporated | Method, system and algorithm related to treatment planning for vision correction |
US7175278B2 (en) * | 2003-06-20 | 2007-02-13 | Visx, Inc. | Wavefront reconstruction using fourier transformation and direct integration |
DE102004033819B8 (de) * | 2004-07-13 | 2011-11-10 | Wavelight Gmbh | Verfahren zum Erzeugen von Steuerdaten eines Lasersystems für ophthalmologische Eingriffe |
UA80467C2 (en) * | 2005-08-31 | 2007-09-25 | Leonid Andriiovych Lynnyk | Method and device for treating macular dystrophy |
EP3115016B1 (de) | 2006-01-06 | 2019-02-27 | Dentsply Implants NV | Dentales handstück |
EP1854438B1 (de) | 2006-05-09 | 2018-07-04 | IROC Services AG | Ophthalmologische Vorrichtung zur Vorbeugung einer Myopie |
DE102006030219A1 (de) | 2006-06-30 | 2008-01-03 | Iroc Ag | Bestrahlungssystem für medizinische Anwendungen |
US10729585B2 (en) | 2006-07-19 | 2020-08-04 | Alcon Inc. | Computer program for ophthalmological surgery |
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- 2009-09-10 ES ES09778460.7T patent/ES2529749T3/es active Active
- 2009-09-10 WO PCT/EP2009/006579 patent/WO2010028830A1/de active Application Filing
- 2009-09-10 EP EP09778460.7A patent/EP2334269B1/de active Active
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Also Published As
Publication number | Publication date |
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DE102008046834A1 (de) | 2010-03-18 |
WO2010028830A8 (de) | 2010-06-03 |
US20110301524A1 (en) | 2011-12-08 |
WO2010028830A1 (de) | 2010-03-18 |
ES2529749T3 (es) | 2015-02-25 |
US8887734B2 (en) | 2014-11-18 |
EP2334269B1 (de) | 2014-12-31 |
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